THE ROLE OF SMALL-INTESTINAL ANTIGEN-PRESENTING CELLS IN THE INDUCTION OF T-CELL REACTIVITY TO SOLUBLE-PROTEIN ANTIGENS - ASSOCIATION BETWEEN ABERRANT PRESENTATION IN THE LAMINA PROPRIA AND ORAL TOLERANCE
Hm. Harper et al., THE ROLE OF SMALL-INTESTINAL ANTIGEN-PRESENTING CELLS IN THE INDUCTION OF T-CELL REACTIVITY TO SOLUBLE-PROTEIN ANTIGENS - ASSOCIATION BETWEEN ABERRANT PRESENTATION IN THE LAMINA PROPRIA AND ORAL TOLERANCE, Immunology, 89(3), 1996, pp. 449-456
The oral administration of soluble protein antigen results in profound
immunological tolerance. However, the tissue location and function of
antigen-presenting cells (APC) that stimulate this response remain un
clear. We have hypothesized that the properties of cells presenting an
tigen to naive T cells within the gut are involved, and therefore gut
APC should stimulate T-cell responses with different characteristics t
o those induced by other APC. To test this, we studied in vitro primar
y T-cell responses following presentation of soluble protein antigen b
y cells from the Peyer's patches (PPC) and lamina propria (LPC) of the
murine small intestine and the spleen (SPLC). Each APC population sti
mulated antigen-specific proliferative responses with similar anamnest
ic characteristics; however, analysis of the cytokines produced reveal
ed marked differences. Whereas SPLC stimulated the balanced production
of T-helper type 1 (Th1) and Th2 cytokines, PPC induced a profile con
sistent with the provision of T-cell help for IgA production. Interest
ingly, presentation of antigen by LPC stimulated high levels of interf
eron-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta)
in the absence of other cytokines [interleukin-2 (IL-2), IL-4, IL-5].
Evidence from analysis of cell activation and division within the cult
ures suggested that this profile may result from the preferential acti
vation of CD8(+) T cells by LPC; however, the lack of conventional CD4
(+) T-cell cytokines indicated a defect in the normal function of thes
e cells. Adoptive transfer of antigen-pulsed LPC to syngeneic animals
abrogated the induction of delayed-type hypersensitivity (DTH) respons
iveness, which followed a subsequent conventional antigen challenge fu
rther suggesting a role for lamina propria APC in tolerance induction.